Various Delta-9-tetrahydrocannabinol effects on human and animal reproduction have been reported. The pattern and level of mature animal gonadotropin secretion are altered by this drug. Neither the anatomical site nor the molecular processes affected in these drug actions are known. The establishment of a pulsatile pattern of hypothalamic neurochemical activity resulting in corresponding discharges of gonadotropin releasing hormone is known to be critical to puberty onset, and to the continued normal pituitary release of gonadotropic hormones. Catecholamines and catecholestrogens are indicated to be modulators in these hypothalamic activities. Studies predominantly utilizing male animals have not established clear relationships between cannibionids and hypothalamic catecholamines or catecholestrogens. Four experiments are proposed in the prepubertal female rat to examine inter-relationships between the above observations. Experiment 1 is designed to indicate Delta-9-tetrahydrocannabinol (1, 2,.5, 5, and 10* mg/kg BW, s.c.; twice daily from 12 days postpartum, 0800 and 1700 h, or acute*) dose-response effects on: 1) prepubertal (15-37 days of age) gonadotropin and prolactin levels; 2) accompanying hypothalamic estrogen metabolism, and; 3) morphological and physiological development of reproductive tissues. Experiment 2 will utilize a chronic drug dose selected from experiment 1 to observe drug effects on the establishment of pulsatile luteinizing hormone secretion, and upon associated hypothalamic norepinephrine and dopamine levels. In a parallel protocol, experiment 3 will observe the drug's effect upon the responsiveness of the prepubertal hypothalamo-pituitary complex to estradiol feedback. Experiment 4 will seek additional data relative to the site and mechanism of the drug's alteration of hypothalamic function through determining its effects on norepinephrine and dopamine turnover rates in this tissue. Radioimmuno- and radioenzymatic assay techniques will be used to quantitate hormones and catechols. The health-relatedness of this study is obvious if the current use of cannabinoids by adolescents is considered.